rs757209133
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_205836.3(FBXO38):c.2423C>T(p.Pro808Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,613,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P808P) has been classified as Likely benign.
Frequency
Consequence
NM_205836.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBXO38 | NM_205836.3 | c.2423C>T | p.Pro808Leu | missense_variant | 15/22 | ENST00000340253.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBXO38 | ENST00000340253.10 | c.2423C>T | p.Pro808Leu | missense_variant | 15/22 | 5 | NM_205836.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152100Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 251020Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135676
GnomAD4 exome AF: 0.0000397 AC: 58AN: 1461832Hom.: 0 Cov.: 32 AF XY: 0.0000413 AC XY: 30AN XY: 727214
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152100Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74292
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 22, 2021 | The p.P808L variant (also known as c.2423C>T), located in coding exon 14 of the FBXO38 gene, results from a C to T substitution at nucleotide position 2423. The proline at codon 808 is replaced by leucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Distal hereditary motor neuropathy type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2023 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 808 of the FBXO38 protein (p.Pro808Leu). This variant is present in population databases (rs757209133, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with FBXO38-related conditions. ClinVar contains an entry for this variant (Variation ID: 541010). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FBXO38 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at